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Cytokines expressed in multinucleated cells: Paget's disease and giant cell tumors versus normal bone.

Human osteoclasts are well characterized multinucleated cells whose function is the directed resorption of normal bone (NB). Osteoclastic bone destruction accompanies lytic solid tumors and myeloma as well as Paget's disease (PD) of bone and giant cell tumors of bone (GCTB). The mechanism of this stimulation of osteoclastic bone resorption is unknown. This study was designed to detect cytokines present in the multinucleated cells of PD and GCTB in order to determine whether cytokine abnormalities exist to account for bone lysis. Nine cytokines, representing the functions of bone resorption, angiogenesis, tumor necrosis, bone cell proliferation, and osteoblast-osteoclast coupling, were examined by immunohistochemistry using tissue samples from 15 NB, 17 PD, and 19 GCTB patients. Standard nonparametric statistical analysis showed a significant increase (P < 0.01 to 0.05) in immunostaining between osteoclasts of PD and NB for interleukin-6 (Il-6), tumor necrosis factor beta (TNFbeta), epidermal growth factor (EGF), platelet derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). There was a statistically significant decrease in immunostaining of giant cells of GCTB as compared with NB for transforming growth factor beta (TGFbeta), but no other differences from normal osteoclasts. The increase in staining of PD osteoclasts over the giant cells of GCTB was significant (P < 0.01) for Il-6, TNFbeta, PDGF, bFGF and insulin growth factor-1 (IGF-1), and (P < 0. 05) for Il-1 and EGF. It was concluded that marked cytokine differences exist in vivo between osteoclasts of NB and PD lesions consistent with stimulated resorption. Alternatively, "osteoclastoma" cells in the center of the tumor did not overexpress the cytokines associated with bone lysis, suggesting some other mechanism for stimulated resorption.

Adolescent↗

Landscape metrics for assessment of landscape destruction and rehabilitation.

This investigation tested the usefulness of geometry-based landscape metrics for monitoring landscapes in a heavily disturbed environment. Research was carried out in a 75 sq km study area in Saxony, eastern Germany, where the landscape has been affected by surface mining and agricultural intensification. Landscape metrics were calculated from digital maps (1912, 1944, 1973, 1989) for the entire study area and for subregions (river valleys, plains), which were defined using the original geology and topography of the region. Correlation and factor analyses were used to select a set of landscape metrics suitable for landscape monitoring. Little land-use change occurred in the first half of the century, but political decisions and technological developments led to considerable change later. Metrics showed a similar pattern with almost no change between 1912 and 1944, but dramatic changes after 1944. Nonparametric statistical methods were used to test whether metrics differed between river valleys and plains. Significant differences in the metrics for these regions were found in the early maps (1912, 1944), but these differences were not significant in 1973 or 1989. These findings indicate that anthropogenic influences created a more home geneous landscape.

Animals↗

Chorioamnionitis risk and neonatal outcome in preterm premature rupture of membranes.

OBJECTIVE: The objective of this study was to compare the neonatal outcome in patients with preterm premature rupture of membranes with and without clinical chorioamnionitis. STUDY DESIGN: This is a retrospective study that included 254 pregnant women with preterm rupture of membranes. The study group was divided according to the presence or absence of clinical chorioamnionitis defined as the presence of two or more of the following criteria: maternal temperature >38 degrees C on two or more occasions > or =1 h apart, maternal tachycardia (> or =120 beats/min), uterine tenderness, foul smelling amniotic fluid, maternal leukocytosis > or =20,000 mm(-3) with bands and positive C reactive protein. Also the study population was divided according to the use of tocolysis. Exclusion criteria included multiple pregnancy, fetal congenital anomalies, diabetes mellitus and severe preeclampsia. Amniotic fluid was collected from the cervix or from the transabdominal amniocentesis. Antibiotics and tocolysis were used according to the hospital protocols. Parametric and nonparametric statistics were used for comparisons. RESULTS: There were no significant differences in birth weight, Apgar scores at 1 and 5 min, rates of respiratory distress syndrome, intraventricular hemorrhage and necrotizing enterocolitis between patients with and without clinical chorioamnionitis or between women who received tocolysis and the ones that did not receive tocolysis. In cases of clinical chorioamnionitis and when tocolysis was used the neonates stayed longer in the neonatal intensive care unit (NICU). CONCLUSION: Patients with preterm premature rupture of membranes and clinical chorioamnionitis have similar neonatal outcomes than the ones without clinical chorioamnionitis.

Adolescent↗

Objective acoustic and aerodynamic measures of breathiness in paralytic dysphonia.

This study was designed to determine which objective acoustic or aerodynamic parameters allowed a homogeneous group of patients with unilateral vocal fold paralysis (UVFP) to be distinguished from an age-matched and smoking-matched control group and to search for linear correlations between the objective parameters and the subjective breathiness ratings. Eight patients with recent-onset UVFP and 12 controls were prospectively studied. The acoustic parameters measured for the vowel /a/ at a comfortable frequency and intensity were: jitter, shimmer, harmonics-to-noise ratio, cepstral peak prominence, the difference between the levels of the first two harmonics and the relative energy above 6 kHz. Aerodynamic parameters included the mean flow rate during a sustained /a/ and intraoral pressure during the production of the phoneme /pi/. The long-term average spectrum was calculated for 40 s of text, and the relative average energies in four frequency bands were compared. Six judges rated a mid-/a/ sample using a five-parameter scale with four levels of severity. Nonparametric statistical analysis revealed significant differences ( P<.05) between the UVFP group and the control group for 14 of the 19 parameters studied. Correlations between the objective parameters and perceived breathiness differed in the two groups. Correlations were not always as expected as based on previous literature reports. These measurements provided an objective qualification of voice in patients with UVFP and successfully distinguished them from the normal controls. The objective acoustic and aerodynamic measurements had generally low linear correlations with breathiness ratings in the control group. Higher correlations were seen in the UVFP group, in which breathiness was best correlated with airflow measurements.

Aged↗

The full-field temporal contrast sensitivity test for glaucoma: influence of cataract.

PURPOSE: To determine the influence of lens opacities on temporal contrast sensitivity, measured by the full-field flicker test ("Erlangen flicker test"). METHODS: Thirty-six consecutive patients (mean age 71.1+/-11.6 years, 12 male, 24 female, refractive error -1.5+/-3.8 dpt) with cataract (visual acuity 0.21+/-0.16, retinal acuity 0.56+/-0.32, no glaucoma) were studied. Temporal contrast sensitivity (full-field flicker test, 37.1 Hz) and lens opacity (back scatter Lens Opacity Meter, Interzeag) were measured preoperatively and on the 3rd postoperative day. STATISTICS: nonparametric tests (Wilcoxon-test, Spearman correlation coefficient, Mann-Whitney U-test). RESULTS: No significant difference was seen in temporal contrast sensitivity pre- and postoperatively, but there was a significant difference in lens opacity measurements pre- and postoperatively. No significant correlation was found between temporal contrast sensitivity and lens opacity values preoperatively and postoperatively. CONCLUSION: The temporal contrast sensitivity, measured by the full-field flicker test, seems to be independent of lens opacity due to the range of cataract included in this study. The data indicate that the full-field flicker test is useful for early glaucoma detection even in patients with cataract formations.

Aged↗

Characteristics of dysphagia in elderly patients requiring mechanical ventilation.

The purpose of this study was to describe the swallowing characteristics of elderly patients requiring mechanical ventilation with tracheostomy admitted to a long-term, acute-care hospital. The study was conducted through retrospective record review of patients on mechanical ventilation who had received a Modified Barium Swallow Study (MBSS) during their hospitalization. In a period from 1994 to 2002, 58 patients met the inclusion criteria. The study examined the results of both the clinical and the MBSS evaluations and compared the results and recommendations of the two examinations. Data were obtained from the MBSS records to describe the group in terms of dysphagia symptoms, frequency and occurrence of aspiration, respiratory status, and demographic variables. Parametric and nonparametric statistics were used to determine differences between the evaluations and any significant associations between aspiration and demographic variables, pharyngeal symptoms, and cognitive deficits. Significant differences were found between diet recommendations before and after the MBSS, and significant associations were found between aspiration and three pharyngeal symptoms. Although aspiration and especially silent aspiration occurred frequently in this group, most individuals were able to begin some level of oral intake after the MBSS evaluation. Due to the lack of reliable clinical evaluation measures, the MBSS is necessary for differential diagnosis of dysphagia and dietary recommendations for these individuals.

Adult↗

Sound component duration of healthy human pharyngoesophageal swallowing: a gender comparison study.

Cervical auscultation is a noninvasive technique for studying swallowing that was first used in the 1960s. The aim of our study was to use the numeric acoustic recording technique for analyzing swallowing sound signals in healthy subjects while they ingested a defined volume and consistency of a specific substance. Twenty males and ten females were included in the study and given 10 ml of a barium suspension to swallow. A microphone was placed on the skin overlying the lateral border of the trachea, directly under the inferior border of the cricoid, and connected to a computer. For each sound recording, the total duration of the sound (td), the number (n) of sound components (SC), the duration of each SC (c1, c2, c3,...), and the intervals (i1, i2,...) between the SCs were measured. For all the recordings, the mean durations of acoustic parameters (TDm, C1m, C2m, C3m, I1m, I2m) were calculated and compared by using Student's t test. In the 20 male subjects, the mean acoustic parameters were calculated (MTDm, MC1m, MC2m, MC3m, MI1m, MI2m) and compared with the mean acoustic parameters (FTDm, FC1m, FC2m, FC3m, FI1m, FI2m) in the ten females by using a Wilcoxon nonparametric statistical test. We were able to interpret 80% of the recordings. The TDm was 710 +/- 28 ms. Three main SCs were detected: C1m = 100 +/- 56, C2m = 150 +/- 90, C3m = 80 +/- 54 ms; I1m = 100 +/- 66, I2m = 190 +/- 120 ms. No significant difference in these parameters was observed with respect to gender. This study enabled us to decompose the swallowing sounds into three main SCs and to quantify their normal durations. These results should prove useful for the assessment of sound variations in pathologic conditions.

Acoustics↗

Ab initio structure of human seminal plasma prostatic inhibin gives significant insight into its biological functions.

Human seminal plasma prostatic inhibin (HSPI) is a protein isolated from the human prostate gland. Despite its profound biomedical and biotechnological importance, the 3D structure of this protein of 94 amino acids remains undeciphered. The difficulties in extracting it in pure form and crystallizing it have restrained the determination of its structure experimentally. The homology-based computational methods are also not applicable, as HSPI lacks sufficient sequence homology with known structures in the protein data banks. We have predicted the structure of HSPI by a knowledge-based method using nonparametric multivariate statistical techniques. Stereochemical and other standard validation tests confirm this to be a well-refined structure. The biophysical properties exhibited by this structure are in good agreement with the NMR experimental observations. Docking and other computational studies on this structure provide significant explanation and insight into its binding activities and related biological and immunogenic functions and offer new directions for its potential applications.

Binding Sites↗

A mixture model approach to detecting differentially expressed genes with microarray data.

An exciting biological advancement over the past few years is the use of microarray technologies to measure simultaneously the expression levels of thousands of genes. The bottleneck now is how to extract useful information from the resulting large amounts of data. An important and common task in analyzing microarray data is to identify genes with altered expression under two experimental conditions. We propose a nonparametric statistical approach, called the mixture model method (MMM), to handle the problem when there are a small number of replicates under each experimental condition. Specifically, we propose estimating the distributions of a t -type test statistic and its null statistic using finite normal mixture models. A comparison of these two distributions by means of a likelihood ratio test, or simply using the tail distribution of the null statistic, can identify genes with significantly changed expression. Several methods are proposed to effectively control the false positives. The methodology is applied to a data set containing expression levels of 1,176 genes of rats with and without pneumococcal middle ear infection.

Animals↗

Binding of synthetic double-stranded DNA by serum from patients with systemic lupus erythematosus: correlation with renal histology.

Detection of antibody to double-stranded DNA by direct binding assays has proved useful in clinical management of patients with systemic lupus erythematosus (SLE). Recent confusion regarding specificity of these antibodies for SLE appears to be due, at least in part, to contamination of natural DNA preparations with nondouble-stranded DNA antigens. Measurement of binding of a synthetic, self-complementary DNA copolymer (dAT) rather than of natural DNA (KB) has been shown to obviate some of these difficulties, apparently because of freedom of dAT from nondouble-stranded DNA antigens. Among the advantages found in this way was a higher degree of specificity of antibodies to double-stranded DNA for clinically-judged active lupus nephritis than had been suspected. Since activity of nephritis is difficult to assess clinically, histologic data were sought to confirm these observations. Thirty-two kidney specimens were examined by light and/or electron microscopy. The degree of histologic activity and the amount and location of glomerular electron-dense deposits were semiquantitated blindly. The binding of both dAT and KB DNA was measured by the ammonium sulfate method. Correlation with the amount of electron-defense deposits was highly significant for dAT binding and somewhat less so for KB DNA binding as determined by both parametric and nonparametric statistical methods. Significant correlation with histologic activity was found for dAT but not KB DNA binding. These results are consistent with previous data and suggest that dAT binding may provide a useful, noninvasive means of clinically assessing both nephritis activity and the intensity of glomerular immune-complex deposition as reflected by the amount of electron-dense deposits. If it can be confirmed that the latter provides long-term prognostic information, then dAT binding (and perhaps its reponse to therapy) may also prove of value in this regard.

Adenosine Monophosphate↗

Early pregnancy changes in hemodynamics and volume homeostasis are consecutive adjustments triggered by a primary fall in systemic vascular tone.

OBJECTIVE: The purpose of this study was to test the hypothesis that early pregnancy changes in volume homeostasis develop as a consequence of preceding changes in maternal hemodynamics. STUDY DESIGN: Maternal cardiovascular function of 10 pregnant women was followed up by Doppler echocardiography. Vascular filling state and volume homeostasis were evaluated by echocardiographic index values, glomerular filtration rate, serum osmolality, and volume-regulating hormones. Studies were performed weekly in early pregnancy, in the second and third trimesters, and post partum. Changes relative to the fifth week and the consistency of changes between weeks 5 and 8 were evaluated by nonparametric statistics. RESULTS: In early pregnancy cardiac output increased and afterload decreased. Concomitant increases in ultrasonic preload index values and glomerular filtration rate were accompanied by decreases in serum renin, Na+, and osmolality. CONCLUSION: These data support the concept that maternal hemodynamic adaptation to pregnancy is most likely triggered by a primary fall in systemic vascular tone. The resulting rapid fall in preload and afterload leads to a compensatory increase in heart rate and activation of the volume-restoring mechanisms. Subsequently cardiac output increases because of a rise in stroke volume, which develops because the vascular filling state normalizes, whereas the reduced afterload reduction is maintained.

Adult↗

A prospective, double-blind, randomized comparison of prophylactic intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, and intravenous oxytocin, 20 units, for the control of blood loss at elective cesarean section.

OBJECTIVE: Our purpose was to compare intramyometrial 15-methyl prostaglandin F2 alpha with intravenous oxytocin for controlling blood loss at elective cesarean section. STUDY DESIGN: A double-blind, randomized trial was performed with intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, or intravenous oxytocin, 20 U, in 60 women undergoing elective lower segment cesarean section at 36 to 41 weeks' gestation. Subjective assessment of the operative blood loss and early lochial discharge and objective change in hemoglobin and hematocrit before and 24 hours after delivery and the incidence of side effects were compared by nonparametric statistical tests. RESULTS: The mean estimated blood loss was similar in both groups, with 645 ml (SD 278, range 400 to 1500) in the 15-methyl prostaglandin F2 alpha group compared with 605 ml (SD 303, range 200 to 1750) in the oxytocin group. The mean fall in hemoglobin and hematocrit was greater in the 15-methyl prostaglandin F2 alpha group than in the oxytocin group, 0.98 gm/dl (SD 0.95) versus 0.65 gm/dl (SD 0.79) for hemoglobin and 2.58% (SD 2.96) versus 2% (SD 2.96) for hematocrit. None of these differences reached statistical significance. There were no differences in side effects and lochial discharge between the treatment groups. In both groups there was a decrease of approximately 1% in maternal arterial oxygen saturation. CONCLUSION: Routine intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, does not offer any obvious advantage over intravenous oxytocin, 20 U, in reducing operative blood loss at elective lower-segment cesarean section.

Adult↗

Hemodynamic effects of different pacing ratios in chronic dynamic double cardiomyoplasty.

BACKGROUND: Dynamic cardiomyoplasty is being used clinically worldwide, and evaluated by a clinical trial (phase III) in the United States. Some centers stimulate the skeletal muscle wrap with every heart beat (1:1 [muscle:heart]), whereas others use every other heart beat (1:2). Recent concern over the possible deleterious effects of too-frequent stimulation of the muscles motivated the attempt to evaluate, in a canine model of chronic, double cardiomyoplasty, the effects of two different pacing ratios on several hemodynamic parameters of interest. METHODS: Double cardiomyoplasty was performed using both latissimus dorsi muscles in 11 dogs. Fatigue resistance was achieved using the clinical transformation protocol. At a final experiment, acute cardiac failure was induced by administration of propranolol. Hemodynamic measurements of eight physiologic variables were averaged over complete pacing cycles, including the nonpaced beat at a 1:2 pacing ratio. RESULTS: The net effects of latissimus dorsi muscle stimulation at each of two pacing ratios were compared using nonparametric statistics. With the exception of left ventricular pressure (p = 0.0262) and its first derivative, dP/dt (p = 0.0099), there was no significant difference between hemodynamic performance at the two pacing ratios. CONCLUSIONS: In this canine model, pacing every other beat produces hemodynamic results that are statistically similar to pacing every beat. Less frequent stimulation of the latissimus dorsi muscle may preserve its function and improve clinical results without compromising hemodynamic benefit.

Acute Disease↗

Predicting stroke inpatient rehabilitation outcome using a classification tree approach.

A classification tree, a nonparametric statistical analysis, was used to develop decision rules to predict a favorable inpatient stroke rehabilitation outcome. Descriptive and functional status data collected on admission from 225 patients were the predictor variables. Favorable outcome was defined as having met three criteria: discharged to community, survival greater than 3 months postdischarge, and no more than minimal physical assistance required in functional activities on discharge. The classification tree correctly classified 88% of the sample using only four of the predictor variables (level of independence in Toilet Management, Bladder Management, and Toilet Transfer, and adequacy of Financial Resources). The cross validation error rate was 18%. The advantages of the classification tree approach over parametric methods are that it is desirable for ordinal data, it readily identifies the interactions among predictor variables, the results are easily communicated, and it provides additional insights into the factors that predict outcome.

Activities of Daily Living↗

Two-sample Kolmogorov-Smirnov test for truncated data.

A nonparametric statistical test to compare two cumulative frequency distribution functions is presented that can be used even when both samples include censored data, as is often the case when comparing the survival of two groups of laboratory animals under conditions in which the experiment is terminated before all the animals die. (Such a design can produce considerable savings and is to be recommended.) The program calculates exact probabilities for both the one-sided and two-sided alternatives to the null hypothesis, applicable to the case of equal group size, as well as the corresponding general asymptotic values; a continuity correction is employed that markedly improves the asymptotic approximation. Expressions are stated in terms of two different but related statistics, and the one that utilizes more information in any particular set of data is selected for the probability calculations. All basic equations and definitions are provided.

Animals↗

Marginal seal of new-generation dental bonding agents.

This in vitro study evaluated microleakage of three new adhesive systems--All-Bond 2, Gluma 2000, and Scotchbond Multi-Purpose. Enamel was removed from the buccal surfaces of 40 extracted molars, and cavity preparations were made on both the buccal and lingual surfaces of each tooth. Buccal cavities were entirely in dentin, and the lingual cavities had enamel margins. Specimens were randomly assigned to three groups for treatment with All-Bond 2, Gluma 2000, or Scotchbond Multi-Purpose adhesive systems. A fourth group of specimens was untreated to serve as the control. All cavity preparations were restored with a visible light-cured microfilled composite resin. Specimens were thermocycled and subjected to a crystal violet staining technique to detect marginal microleakage. Microleakage was recorded as ordinal data and analyzed with nonparametric statistical tests. Each of the adhesives tested significantly reduced microleakage at the enamel and dentin margins. The extent of leakage at dentin margins was only slightly greater than at enamel margins in each treatment group.

Adhesives↗

Influence of tapping-time and atmospheric pressure on concentrations of monoamine metabolites in the cerebrospinal fluid: a prospective study in female volunteers.

Lumbar puncture was performed on 12 healthy female volunteers at the L4-5 level. CSF concentrations of 5-HIAA, HVA and HMPG were included in turn as dependent variables in repeated analyses of covariance with age, height, tapping-time, atmospheric pressure and the distance on the spine in the lying position as regressors. Use or non-use of oral contraceptives was included as a nominal variable. Results obtained were confirmed by nonparametric statistics. We found significant relationships between 5-HIAA and HVA, respectively, and height when the concentrations per minute of tapping-time (nM/min) were used as dependent variables. Hypothetically, the tapping-time mirrors the transport of concentrated CSF from the cranial to the caudal region when sitting up. We also found significant influences of atmospheric pressure and the use or non-use of oral contraceptives on HMPG. The role of atmospheric pressure is not clear but it might contribute to the transport of HMPG from the periphery to the CSF or affect the outflow of HMPG from the lumbar CSF compartment. The contribution of oral contraceptives might reflect interactions in the cerebral catecholamine metabolism.

Adult↗

Growth hormone (GH)-releasing effects of synthetic peptide GH-releasing peptide-2 and GH-releasing hormone (1-29NH2) in children with GH insufficiency and idiopathic short stature.

To investigate how growth hormone (GH)-releasing peptide (GHRP) and GH-releasing hormone (GHRH) interact in patients with short stature, we examined the acute effects of GHRH1-29NH2, GHRP-2, and the combination of GHRH1-29NH2 and GHRP-2 on GH release in children with GH insufficiency ([GHI] group A) and idiopathic short stature ([ISS] group B). Ten children with GHI (aged 11.8 +/- 1.1 years; height, -4.2 +/- 0.5 SDS) and five children with ISS (aged 11.1 +/- 1.2 years; height, -3.2 +/- 0.1 SDS) were studied. Intravenous bolus infusions of GHRH1-29NH2 (1 micrograms/kg), GHRP-2(1 microgram/kg), and GHRH plus GHRP-2 (each 1 micrograms/kg), were administered in a randomized order. Because of the variability of GH responses, results were analyzed by a nonparametric statistical method. Patients in group A showed low GH responses to both GHRH1-29NH2 and GHRP-2 stimulation: in only three of 10 and one of nine cases, respectively, were the peak GH levels above 5.0 micrograms/L. GH area under the curve (AUC) 90 minutes after GHRP-2 administration was slightly less than for GHRH1-29NH2 (179 +/- 150 v 214 +/- 68 micrograms/L.min, P = .06). In group B, GH responses to GHRH1-29NH2 and GHRP-2 were approximately of the same magnitude (1,943 +/- 819 v 1,981 +/- 887 micrograms/L.min, P = .9).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗